In the fluorescent equilibrium state, we find that the chromophore adopts exclusively the cis isomeric form. Surprisingly, the chromophore environment of Dronpa is almost identical to that of KikG, a fluorescent protein that does not exhibit photoswitching. Furthermore, we find structural similarities to asFP595 that point to a cis–trans isomerization of the chromophore as a key event in photochromic switching. Based on this assumption and the obtained structural information we generated rsFastLime (Dronpa-V157G) and Dronpa-M159T [aka Dronpa-2], two variants that exhibit strongly accelerated switching kinetics. Our findings support the view of a photoinduced cis–trans isomerization of the chromophore in Dronpa.